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Journal of Autism and Developmental Disorders

, Volume 39, Issue 7, pp 1079–1086 | Cite as

Brief Report: Biochemical Correlates of Clinical Impairment in High Functioning Autism and Asperger’s Disorder

  • Natalia M. KleinhansEmail author
  • Todd Richards
  • Kurt E. Weaver
  • Olivia Liang
  • Geraldine Dawson
  • Elizabeth Aylward
Brief Report

Abstract

Amygdala dysfunction has been proposed as a critical contributor to social impairment in autism spectrum disorders (ASD). The current study investigated biochemical abnormalities in the amygdala in 20 high functioning adults with autistic disorder or Asperger’s disorder and 19 typically developing adults matched on age and IQ. Magnetic resonance spectroscopy was used to measure N-acetyl aspartate (NAA), creatine/phosphocreatine (Cre), choline/choline containing compounds (Cho), and Myoinositol (mI) in the right and left amygdala. There were no significant between-group differences in any of the metabolites. However, NAA and Cre levels were significantly correlated to clinical ratings on the Autism Diagnostic Interview-Revised. This suggests that altered metabolite levels in the amygdala may be associated with a more severe early developmental course in ASD.

Keywords

Amygdala Autism Asperger’s disorder MRS 

Notes

Acknowledgments

This work was supported by the National Institute of Child Health and Human Development (U19 HD34565) and the National Institute of Mental Health (U54MH066399).

References

  1. Adolphs, R. (2001). The neurobiology of social cognition. Current Opinion in Neurobiology, 11(2), 231–239. doi: 10.1016/S0959-4388(00)00202-6.PubMedCrossRefGoogle Scholar
  2. Adolphs, R., Sears, L., & Piven, J. (2001). Abnormal processing of social information from faces in autism. Journal of Cognitive Neuroscience, 13(2), 232–240. doi: 10.1162/089892901564289.PubMedCrossRefGoogle Scholar
  3. Adolphs, R., Tranel, D., Hamann, S., Young, A. W., Calder, A. J., Phelps, E. A., et al. (1999). Recognition of facial emotion in nine individuals with bilateral amygdala damage. Neuropsychologia, 37(10), 1111–1117. doi: 10.1016/S0028-3932(99)00039-1.PubMedCrossRefGoogle Scholar
  4. Amaral, D. G., Bauman, M. D., & Schumann, C. M. (2003). The amygdala and autism: Implications from non-human primate studies. Genes Brain & Behavior, 2(5), 295–302. doi: 10.1034/j.1601-183X.2003.00043.x.CrossRefGoogle Scholar
  5. Amat, J. A., Bansal, R., Whiteman, R., Haggerty, R., Royal, J., & Peterson, B. S. (2008). Correlates of intellectual ability with morphology of the hippocampus and amygdala in healthy adults. Brain and Cognition, 66(2), 105–114. doi: 10.1016/j.bandc.2007.05.009.PubMedCrossRefGoogle Scholar
  6. Ashwin, C., Baron-Cohen, S., Wheelwright, S., O’Riordan, M., & Bullmore, E. T. (2006). Differential activation of the amygdala and the ‘social brain’ during fearful face-processing in Asperger Syndrome. Neuropsychologia, 1, 349–363.Google Scholar
  7. Aylward, E. H., Minshew, N. J., Field, K., Sparks, B. F., & Singh, N. (2002). Effects of age on brain volume and head circumference in autism. Neurology, 59(2), 175–183.PubMedGoogle Scholar
  8. Aylward, E. H., Minshew, N. J., Goldstein, G., Honeycutt, N. A., Augustine, A. M., Yates, K. O., et al. (1999). MRI volumes of amygdala and hippocampus in non-mentally retarded autistic adolescents and adults. Neurology, 53(9), 2145–2150.PubMedGoogle Scholar
  9. Bachevalier, J., & Loveland, K. A. (2006). The orbitofrontal-amygdala circuit and self-regulation of social-emotional behavior in autism. Neuroscience and Biobehavioral Reviews, 30(1), 97–117. doi: 10.1016/j.neubiorev.2005.07.002.PubMedCrossRefGoogle Scholar
  10. Barker, P. B., Soher, B. J., Blackband, S. J., Chatham, J. C., Mathews, V. P., & Bryan, R. N. (1993). Quantitation of proton NMR spectra of the human brain using tissue water as an internal concentration reference. NMR in Biomedicine, 6(1), 89–94. doi: 10.1002/nbm.1940060114.PubMedCrossRefGoogle Scholar
  11. Baron-Cohen, S., Ring, H. A., Bullmore, E. T., Wheelwright, S., Ashwin, C., & Williams, S. C. (2000). The amygdala theory of autism. Neuroscience and Biobehavioral Reviews, 24(3), 355–364. doi: 10.1016/S0149-7634(00)00011-7.PubMedCrossRefGoogle Scholar
  12. Baron-Cohen, S., Ring, H. A., Wheelwright, S., Bullmore, E. T., Brammer, M. J., Simmons, A., et al. (1999). Social intelligence in the normal and autistic brain: An fMRI study. The European Journal of Neuroscience, 11(6), 1891–1898. doi: 10.1046/j.1460-9568.1999.00621.x.PubMedCrossRefGoogle Scholar
  13. Brooks, W. M., Friedman, S. D., & Stidley, C. A. (1999). Reproducibility of 1H-MRS in vivo. Magnetic Resonance in Medicine, 41(1), 193–197. doi: 10.1002/(SICI)1522-2594(199901)41:1<193::AID-MRM27>3.0.CO;2-P.PubMedCrossRefGoogle Scholar
  14. Courchesne, E., Karns, C. M., Davis, H. R., Ziccardi, R., Carper, R. A., Tigue, Z. D., et al. (2001). Unusual brain growth patterns in early life in patients with autistic disorder: An MRI study. Neurology, 57(2), 245–254.PubMedGoogle Scholar
  15. Critchley, H. D., Daly, E. M., Bullmore, E. T., Williams, S. C., Van Amelsvoort, T., Robertson, D. M., et al. (2000). The functional neuroanatomy of social behaviour: Changes in cerebral blood flow when people with autistic disorder process facial expressions. Brain, 123(Pt 11), 2203–2212. doi: 10.1093/brain/123.11.2203.PubMedCrossRefGoogle Scholar
  16. Dalton, K. M., Nacewicz, B. M., Johnstone, T., Schaefer, H. S., Gernsbacher, M. A., Goldsmith, H. H., et al. (2005). Gaze fixation and the neural circuitry of face processing in autism. Nature Neuroscience, 8(4), 519–526.PubMedGoogle Scholar
  17. Endo, T., Shioiri, T., Kitamura, H., Kimura, T., Endo, S., Masuzawa, N., et al. (2007). Altered chemical metabolites in the amygdala-hippocampus region contribute to autistic symptoms of autism spectrum disorders. Biological Psychiatry, 62(9), 1030–1037. doi: 10.1016/j.biopsych.2007.05.015.PubMedCrossRefGoogle Scholar
  18. Friedman, S. D., Shaw, D. W., Artru, A. A., Richards, T. L., Gardner, J., Dawson, G., et al. (2003). Regional brain chemical alterations in young children with autism spectrum disorder. Neurology, 60(1), 100–107.PubMedGoogle Scholar
  19. Gabis, L., Wei, H., Azizian, A., DeVincent, C., Tudorica, A., Kesner-Baruch, Y., et al. (2008). 1H-magnetic resonance spectroscopy markers of cognitive and language ability in clinical subtypes of autism spectrum disorders. Journal of Child Neurology, 23(7), 766–774. doi: 10.1177/0883073808315423.PubMedCrossRefGoogle Scholar
  20. Jung, R. E., Brooks, W. M., Yeo, R. A., Chiulli, S. J., Weers, D. C., & Sibbitt, W. L., Jr. (1999). Biochemical markers of intelligence: a proton MR spectroscopy study of normal human brain. Proc Biol Sci, 266(1426), 1375–1379. doi: 10.1098/rspb.1999.0790.PubMedCrossRefGoogle Scholar
  21. Jung, R. E., Yeo, R. A., Chiulli, S. J., Sibbitt, W. L., Jr, & Brooks, W. M. (2000). Myths of neuropsychology: intelligence, neurometabolism, and cognitive ability. The Clinical Neuropsychologist, 14(4), 535–545. doi: 10.1076/clin.14.4.535.7198.PubMedGoogle Scholar
  22. Kleinhans, N. M., Richards, T., Sterling, L., Stegbauer, K. C., Mahurin, R., Johnson, L. C., et al. (2008). Abnormal functional connectivity in autism spectrum disorders during face processing. Brain, 131(Pt 4), 1000–1012. doi: 10.1093/brain/awm334.PubMedCrossRefGoogle Scholar
  23. Lord, C., Risi, S., Lambrecht, L., Cook, E., Leventhal, B., DiLavore, P., et al. (2000). The autism diagnostic observation schedule-generic: A standard measure of social and communication deficits associated with the spectrum of autism. Journal of Autism and Developmental Disorders, 30(3), 205–223. doi: 10.1023/A:1005592401947.PubMedCrossRefGoogle Scholar
  24. Lord, C., Rutter, M., & Le Couteur, A. (1994). Autism diagnostic interview-revised: A revised version of a diagnostic interview for caregivers of individuals with possible pervasive developmental disorders. Journal of Autism and Developmental Disorders, 24(5), 659–685. doi: 10.1007/BF02172145.PubMedCrossRefGoogle Scholar
  25. Munson, J., Dawson, G., Abbott, R., Faja, S., Webb, S. J., Friedman, S. D., et al. (2006). Amygdalar volume and behavioral development in autism. Archives of General Psychiatry, 63(6), 686–693. doi: 10.1001/archpsyc.63.6.686.PubMedCrossRefGoogle Scholar
  26. Murphy, D. G., Critchley, H. D., Schmitz, N., McAlonan, G., Van Amelsvoort, T., Robertson, D., et al. (2002). Asperger syndrome: A proton magnetic resonance spectroscopy study of brain. Archives of General Psychiatry, 59(10), 885–891. doi: 10.1001/archpsyc.59.10.885.PubMedCrossRefGoogle Scholar
  27. Nacewicz, B. M., Dalton, K. M., Johnstone, T., Long, M. T., McAuliff, E. M., Oakes, T. R., et al. (2006). Amygdala volume and nonverbal social impairment in adolescent and adult males with autism. Archives of General Psychiatry, 63(12), 1417–1428. doi: 10.1001/archpsyc.63.12.1417.PubMedCrossRefGoogle Scholar
  28. Otsuka, H., Harada, M., Mori, K., Hisaoka, S., & Nishitani, H. (1999). Brain metabolites in the hippocampus-amygdala region and cerebellum in autism: An 1H-MR spectroscopy study. Neuroradiology, 41(7), 517–519. doi: 10.1007/s002340050795.PubMedCrossRefGoogle Scholar
  29. Page, L. A., Daly, E., Schmitz, N., Simmons, A., Toal, F., Deeley, Q., et al. (2006). In vivo 1H-magnetic resonance spectroscopy study of amygdala-hippocampal and parietal regions in autism. American Journal of Psychiatry, 163, 2189–2192.Google Scholar
  30. Pfefferbaum, A., Adalsteinsson, E., Spielman, D., Sullivan, E. V., & Lim, K. O. (1999). In vivo spectroscopic quantification of the N-acetyl moiety, creatine, and choline from large volumes of brain gray and white matter: Effects of normal aging. Magnetic Resonance in Medicine, 41(2), 276–284. doi: 10.1002/(SICI)1522-2594(199902)41:2<276::AID-MRM10>3.0.CO;2-8.PubMedCrossRefGoogle Scholar
  31. Pierce, K., Muller, R. A., Ambrose, J., Allen, G., & Courchesne, E. (2001). Face processing occurs outside the fusiform ‘face area’ in autism: Evidence from functional MRI. Brain, 124(Pt 10), 2059–2073. doi: 10.1093/brain/124.10.2059.PubMedCrossRefGoogle Scholar
  32. Provencher, S. W. (1993). Estimation of metabolite concentrations from localized in vivo proton NMR spectra. Magnetic Resonance in Medicine, 30(6), 672–679. doi: 10.1002/mrm.1910300604.PubMedCrossRefGoogle Scholar
  33. Redcay, E., & Courchesne, E. (2005). When is the brain enlarged in autism? A meta-analysis of all brain size reports. Biological Psychiatry, 58(1), 1–9. doi: 10.1016/j.biopsych.2005.03.026.PubMedCrossRefGoogle Scholar
  34. Schumann, C. M., & Amaral, D. G. (2006). Stereological analysis of amygdala neuron number in autism. The Journal of Neuroscience, 26(29), 7674–7679. doi: 10.1523/JNEUROSCI.1285-06.2006.PubMedCrossRefGoogle Scholar
  35. Schumann, C. M., Hamstra, J., Goodlin-Jones, B. L., Lotspeich, L. J., Kwon, H., Buonocore, M. H., et al. (2004). The amygdala is enlarged in children but not adolescents with autism; The hippocampus is enlarged at all ages. The Journal of Neuroscience, 24(28), 6392–6401. doi: 10.1523/JNEUROSCI.1297-04.2004.PubMedCrossRefGoogle Scholar
  36. Sparks, B. F., Friedman, S. D., Shaw, D. W., Aylward, E. H., Echelard, D., Artru, A. A., et al. (2002). Brain structural abnormalities in young children with autism spectrum disorder. Neurology, 59(2), 184–192.PubMedGoogle Scholar
  37. Wang, A. T., Dapretto, M., Hariri, A. R., Sigman, M., & Bookheimer, S. Y. (2004). Neural correlates of facial affect processing in children and adolescents with autism spectrum disorder. Journal of the American Academy of Child and Adolescent Psychiatry, 43(4), 481–490. doi: 10.1097/00004583-200404000-00015.PubMedCrossRefGoogle Scholar
  38. Watson, D., & Friend, R. (1969). Measurement of social-evaluative anxiety. Journal of Consulting and Clinical Psychology, 33(4), 448–457. doi: 10.1037/h0027806.PubMedCrossRefGoogle Scholar
  39. Williams, J. H., Waiter, G. D., Gilchrist, A., Perrett, D. I., Murray, A. D., & Whiten, A. (2006). Neural mechanisms of imitation and ‘mirror neuron’ functioning in autistic spectrum disorder. Neuropsychologia, 44(4), 610–621. doi: 10.1016/j.neuropsychologia.2005.06.010.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  • Natalia M. Kleinhans
    • 1
    • 3
    • 4
    Email author
  • Todd Richards
    • 1
    • 4
  • Kurt E. Weaver
    • 1
  • Olivia Liang
    • 1
  • Geraldine Dawson
    • 2
    • 3
    • 4
    • 5
  • Elizabeth Aylward
    • 1
    • 3
    • 4
    • 6
  1. 1.Department of RadiologyUniversity of WashingtonSeattleUSA
  2. 2.Department of PsychologyUniversity of WashingtonSeattleUSA
  3. 3.Center on Human Development and DisabilityUniversity of WashingtonSeattleUSA
  4. 4.Autism CenterUniversity of WashingtonSeattleUSA
  5. 5.Autism SpeaksNew YorkUSA
  6. 6.Seattle Children’s Research InstituteSeattleUSA

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